Molecular Markers of Reactive Plasticity

Abstract

Reactive plasticity, including axonal and dendritic sprouting and reactive synaptogenesis, has been proposed to contribute to the pathogenesis of several neurological disorders. We have obtained evidence suggestive of plasticity in Alzheimer’s disease and temporal lobe epilepsy. In each of these disorders, an altered distribution of excitatory amino acid receptors, particularly of the kainic acid subtype, was observed in the hippocampal formation (Geddes et al., 1985; Cahan et al., 1987; Geddes et al., submitted). Altered distribution of kainic acid binding sites has also been observed in other forms of childhood epilepsy (Represa et al., 1989). Additional markers of plasticity in human neurological disorders have included intensification of acetylcholinesterase staining in Alzheimer’s disease (Geddes et al., 1985), and supragranular Timm’s staining in temporal lobe epilepsy (Babb et al., 1988). Although these results are suggestive of sprouting, this interpretation is open to question. The increase in receptor density could simply be the result of receptor upregulation. The intensification of Timm’s staining could result from increased zinc in existing terminals, and intensification of acetylcholinesterase staining is also relatively nonspecific. In addition to their lack of specificity, many of the morphological methods used to demonstrate sprouting in the rodent brain are unsuitable for use in postmortem human tissue. For example, Timm staining requires perfusion with a sulfide solution for optimal results.